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Combination Trial of Tipifarnib and Alpelisib in Adult Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)

Sponsor
Kura Oncology, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04997902
Collaborator
(none)
40
Enrollment
11
Locations
2
Arms
32.8
Anticipated Duration (Months)
3.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase 1/2 combination trial of tipifarnib, a farnesyltransferase inhibitor, and alpelisib, a PI3K inhibitor in participants with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) whose tumors overexpress the HRAS protein and/or are PIK3CA-mutated and/or PIK3CA-amplified.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
40 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Open-label, Biomarker-defined Cohort Trial to Evaluate the Safety, Determine the Recommended Combination Dosing, and Assess Early Antitumor Activity of Tipifarnib and Alpelisib for the Treatment of Adult Participants Who Have HRAS-overexpressing and/or PIK3CA-mutated and/or - Amplified Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
Actual Study Start Date :
Dec 7, 2021
Anticipated Primary Completion Date :
Sep 1, 2024
Anticipated Study Completion Date :
Sep 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: PIK3CA-dependent (Cohort 1)

Adult participants with R/M HNSCC whose tumors harbor PI3KCA (activating) mutations and/or amplifications

Drug: Tipifarnib
Oral administration

Drug: Alpelisib
Oral administration
Other Names:
  • BYL719

    		•
    Experimental: HRAS-dependent (Cohort 2)

    Adult participants with R/M HNSCC whose tumors have increased HRAS dependency, defined as HRAS overexpression

    Drug: Tipifarnib
    Oral administration

    Drug: Alpelisib
    Oral administration
    Other Names:
  • BYL719

    		•

    Outcome Measures

    Primary Outcome Measures

    1. To determine the recommended dose and regimen and evaluate the safety and tolerability of the combination of tipifarnib and alpelisib [DLTs will be evaluated during the first 28 days (1 cycle) of combination therapy]

      Rate of DLT per dose level and Descriptive statistics of adverse events per the NCI CTCAE v 5.0

    Secondary Outcome Measures

    1. Determine the Objective Response Rate (ORR) [Up to approximately 3 years]

      Overall confirmed response rate (CR + PR) and Median duration of response

    2. Disease control rate (DCR) [Up to approximately 3 years]

      Disease control rate (CR + PR + SD), Median duration of disease control, Rate of SD, Median duration of SD

    3. Cmax of tipifarnib and alpelisib when administered in combination [Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.]

      Peak drug concentration for single dose and multiple dose

    4. Tmax of tipifarnib and alpelisib when administered in combination [Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.]

      Time to reach peak concentration following drug administration for single dose and multiple dose

    5. AUC(0-last) of tipifarnib and alpelisib when administered in combination [Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.]

      Area under the concentration-time curve from time zero to time of last measurable concentration for single dose and multiple dose

    6. AUC(tau) of tipifarnib and alpelisib when administered in combination [Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.]

      Area under the concentration-time curve during a dosage interval for single dose and multiple dose

    7. AUC(0-infinity) of tipifarnib and alpelisib when administered in combination [Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.]

      Area under the concentration-time curve from time zero to infinity for single dose

    8. CL/F of tipifarnib and alpelisib when administered in combination [Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.]

      Apparent total clearance of the drug after administration for single dose and multiple dose

    9. Vd/F of tipifarnib and alpelisib when administered in combination [Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.]

      Apparent volume of distribution after administration for single dose and multiple dose

    10. Half-life of tipifarnib and alpelisib when administered in combination [Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.]

      Time required for the amount of drug in the body to decrease by half for single dose and multiple dose

    11. Accumulation ratio of tipifarnib and alpelisib when administered in combination [Blood samples will be collected on day 1 and day 2 of Cycle 1 and Cycle 2, and on day 1 of Cycle 3 through Cycle 6. Each cycle is 28 days.]

      Ratio of accumulation of a drug after multiple doses compared to a single dose

    12. Antitumor activity in terms of PFS and rate of PFS at 6 months [Up to approximately 3 years]

      Median PFS and Proportion of participants alive and without progression at 6 months

    13. Overall Survival (OS) and rate of OS at 12 months [Up to approximately 3 years]

      Median OS and Proportion of participants alive at 12 months

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. At least 18 years of age.

    2. Histologically confirmed head and neck cancer of squamous histology not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).

    3. Documented treatment failure from at least 1 prior systemic therapy in the R/M setting, unless determined not appropriate.

    4. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

    5. Has a tumor that is dependent upon HRAS and/or PIK3CA.

    6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

    7. Acceptable liver, renal, endocrine, and hematologic function.

    8. Must be able to swallow alpelisib whole tablet or oral suspension containing crushed tablets. Feeding tube may not be used for alpelisib administration.

    9. Other protocol defined inclusion criteria may apply.

    Exclusion Criteria:

    1. Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (eg, mucosal melanoma).

    2. Ongoing treatment with certain anticancer agents.

    3. Prior treatment (at least 1 full treatment cycle) with an FTI or PI3K, mTOR, or AKT inhibitor.

    4. Received treatment for unstable angina, myocardial infarction, and/or cerebro-vascular attack within the prior 6 months.

    5. Non-tolerable Grade 2, or ≥ Grade 3 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.

    6. Major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1, without complete recovery.

    7. Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy.

    8. Participant with an established diagnosis of diabetes mellitus Type 1 or not controlled Type 2.

    9. Participant has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the trial drugs based on Investigator discretion.

    10. Participant has currently documented pneumonitis/interstitial lung disease.

    11. Participant has a history of severe cutaneous reaction, such as Stevens-Johnson Syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necrolysis (TEN), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

    12. Other protocol defined exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Comprehensive Cancer Center Duarte California United States 91010
    2 Lake Nona DDU (Florida Cancer Specialists) Orlando Florida United States 32827
    3 University of Maryland School of Medicine (Marlene and Stewart Greenebaum Comprehensive Cancer Center) Baltimore Maryland United States 21201
    4 Johns Hopkins University School of Medicine (Sidney Kimmel Comprehensive Cancer Center) Baltimore Maryland United States 21231
    5 Dana-Farber Cancer Institute (Head and Neck Cancer Treatment Center) Boston Massachusetts United States 02215
    6 Washington University, School of Medicine Saint Louis Missouri United States 63110
    7 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    8 UPMC Hillman Cancer Center Pittsburgh Pennsylvania United States 15232
    9 UT Southwestern Medical Center (Harold C. Simmons Comprehensive Cancer Center) Dallas Texas United States 75390
    10 University of Texas MD Anderson Cancer Center Houston Texas United States 77030
    11 University of Wisconsin Carbone Cancer Center Madison Wisconsin United States 53792

    Sponsors and Collaborators

    • Kura Oncology, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Kura Oncology, Inc.
    ClinicalTrials.gov Identifier:
    NCT04997902
    Other Study ID Numbers:
    • KO-TIP-013
    First Posted:
    Aug 10, 2021
    Last Update Posted:
    Jul 5, 2022
    Last Verified:
    Jun 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Kura Oncology, Inc.
    HRAS
    PIK3CA
    PI3K
    Tipifarnib
    Alpelisib
    R/M HNSCC (Recurrent/metastatic Head and Neck Squamous Cell Carcinoma)
    Head and Neck Cancer
    SCCHN
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Squamous Cell
    Squamous Cell Carcinoma of Head and Neck
    Tipifarnib

    Study Results

    No Results Posted as of Jul 5, 2022